CITK Loss Inhibits Growth of Group 3 and Group 4 Medulloblastoma Cells and Sensitizes Them to DNA-Damaging Agents.

Medulloblastoma (MB) is the most common malignant brain tumor in children, and it is classified into four biological subgroups: WNT, Sonic Hedgehog (SHH), Group 3 and Group 4. The current treatment is surgery, followed by irradiation and chemotherapy. Unfortunately, these therapies are only partially effective. Citron kinase protein (CITK) has been proposed as a promising target for SHH MB, whose inactivation leads to DNA damage and apoptosis. D283 and D341 cell lines (Group 3/Group 4 MB) were silenced with established siRNA sequences against CITK, to assess the direct effects of its loss. Next, D283, D341, ONS-76 and DAOY cells were treated with ionizing radiation (IR) or cisplatin in combination with CITK knockdown. CITK depletion impaired proliferation and induced cytokinesis failure and apoptosis of G3/G4 MB cell lines. Furthermore, CITK knockdown produced an accumulation of DNA damage, with reduced RAD51 nuclear levels. Association of IR or cisplatin with CITK depletion strongly impaired the growth potential of all tested MB cells. These results indicate that CITK inactivation could prevent the expansion of G3/G4 MB and increase their sensitivity to DNA-damaging agents, by impairing homologous recombination. We suggest that CITK inhibition could be broadly associated with IR and adjuvant therapy in MB treatment.

A new approach for the pixel map sensitivity (PMS) evaluation of an electronic portal imaging device (EPID).

When using an electronic portal imaging device (EPID) for dosimetric verifications, the calibration of the sensitive area is of paramount importance. Two calibration methods are generally adopted: one, empirical, based on an external reference dosimeter or on multiple narrow beam irradiations, and one based on the EPID response simulation. In this paper we present an alternative approach based on an intercalibration procedure, independent from external dosimeters and from simulations, and is quick and easy to perform. Each element of a detector matrix is characterized by a different gain; the aim of the calibration procedure is to relate the gain of each element to a reference one. The method that we used to compute the relative gains is based on recursive acquisitions with the EPID placed in different positions, assuming a constant fluence of the beam for subsequent deliveries. By applying an established procedure and analysis algorithm, the EPID calibration was repeated in several working conditions. Data show that both the photons energy and the presence of a medium between the source and the detector affect the calibration coefficients less than 1%. The calibration coefficients were then applied to the acquired images, comparing the EPID dose images with films. Measurements were performed with open field, placing the film at the level of the EPID. The standard deviation of the distribution of the point-to-point difference is 0.6%. An approach of this type for the EPID calibration has many advantages with respect to the standard methods - it does not need an external dosimeter, it is not related to the irradiation techniques, and it is easy to implement in the clinical practice. Moreover, it can be applied in case of transit or nontransit dosimetry, solving the problem of the EPID calibration independently from the dose reconstruction method.

Clinical use of EBT model Gafchromic film in radiotherapy.

The Gafchromic EBT was recently introduced in film dosimetry for external beam therapy (EBT). The high spatial resolution, weak energy dependence, and near-tissue equivalence of EBT films make them suitable for measurement of dose distributions in radiotherapy, especially intensity-modulated radiation therapy (IMRT). Starting with a sensitometric curve and dose uncertainty relative to the flatbed scanner, the goal of this study was to find an efficient method of correcting for light scattering, and to compare dose distribution supplied by Gafchromic EBT with the distribution obtained with a 2D ion-chamber detector system. Light scattering was analyzed for different levels of dose, and was found to depend on the red-scale value as well as the position of the pixel on the scanner. Many "uniform" films were exposed at different levels of dose to create a two-dimensional matrix correction to take this effect into account. The dose distribution obtained for three clinical beams (10 x 10, 15 x 15 cm open fields and 12 x 12 cm wedge 60 degrees field) were in agreement with those supplied by the 2D array. Gamma index <1 (using 5 mm distance and 5% dose as constraints) for the three fields considered was reached in an average of 98% of the points.

Prostate brachytherapy with iodine-125 seeds: radiation protection issues.

AIMS AND BACKGROUND: Brachytherapy for prostate cancer by means of permanently implanted 125I sources is a well established procedure. An increasing number of patients all over the world are treated with this modality. When the technique was introduced at our institution, radiation protection issues relative to this technique were investigated in order to comply with international recommendations and national regulations. Particular attention was paid to the need for patient shielding after discharge from hospital. METHODS: The effective and equivalent doses to personnel related to implantation, the effective dose to patient relatives as computed by a developed algorithm, the air kerma strength values for the radioactive sources certified by the manufacturer compared with those measured by a well chamber, and the effectiveness of lead gloves in shielding the hands were evaluated. RESULTS: The effective dose to the bodies of personnel protected by a lead apron proved to be negligible. The mean equivalent doses to the physician's hands was 420 microSv for one implant; the technician's hands received 65 microSv. The mean air kerma rate measured at the anterior skin surface of the patient who had received an implant was 55 microGy/h (range, 10-115) and was negligible with lead protection. The measured and certified air kerma strength for125I seeds in RAPID Strand corresponded within a margin of +/- 5%. The measured attenuation by lead gloves in operative conditions was about 80%. We also defined the recommendations to be given to the patient at discharge. CONCLUSIONS: The exposure risks related to brachytherapy with 125I to operators and public are limited. However, alternation of operators should be considered to minimize exposure. Patient-related measurements should verify the dose rate around the patient to evaluate the need for shielding and to define appropriate radiation protection recommendations.